The phenomenon of multiple false positive reactions on donor screening tests for HIV-1, HTLV-I, and HCV, and a possible correlation with flu vaccination was first described by kit manufacturers in December, 1991. We obtained aliquots of 64 donor samples which exhibited false positivity in screening tests in the fall of '91. A survey of licensed test kits indicated that the kits of several manufacturers were involved. False positive reactions with these samples ranged from 0- 100% in HIV kits, 2-86% in HTLV kits, and 0-63% in HCV kits. A single anti-HBc kit tested was falsely positive for 23% of the samples. A panel was prepared of pre- and post-vaccination sera from 156 individuals who received the flu vaccine either in 1990-91 or 1991-92. False positive reactions following influenza vaccination were detected with a single HIV test kit at a rate which exceeded that found in clinical surveillance studies. Two panels were also prepared of pre- and post-vaccination sera from 100 individuals each who received hepatitis B vaccine from one of two different manufacturers. For one of the two panels, false positive reactions following hepatitis B vaccination were detected with a single HTLV test kit in 58% of the vaccinees, suggesting that at least some of the cases of false positivity may be correlated with vaccination.